The sperm acrosome reaction (AR) is a Ca2+-dependent exocytotic event that occurs during the early stages of fertilization in many animal species, including humans and all other mammals. One model of the signal transduction mechanisms linking ZP3 stimulation to sustained intracellular calcium (Ca2+i) responses suggests that ZP3 activates two primary signal transducers. First phospholipase C (PLC) activity is stimulated and generates inositol trisphosphate (IP3), leading to activation of IP3-gated Ca2+ release channels in the acrosome. There is also activation of a T-type voltage-sensitive Ca2+ channel that produces a transient Ca2+ influx during the first second of ZP3 signaling. The pivotal role of the AR is indicated by the observation that fertilization fails when exocytosis occurs either prematurely or is inhibited. The TRPC2 (Transient Receptor Potential Classic 2) gene encodes a subunit of a sperm Ca2+ channel; that ZP3, the AR-inducing agonist of the egg's extracellular zona pellucida matrix (henceforth zona) activates the TRPC2 channel to trigger a sustained Ca2+ entry into sperm; and that it is this Ca2+ entry that drives the AR (Jungnickel et al., 2001, Nature Cell Biol. 3:499-502). However, TRPC2 is believed to be a pseudogene in humans.
TRPCs have been implicated to be involved as an ion channel in signal transduction in cell proliferation, activation, immune response, and secretion.